Infectious Diseases 2020

Infectious Diseases 2020

A vaccine approach to prevent infection caused by Campylobacter

Science Advances 24 Jun 2020 27 June, 2020

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide. C. jejuni is a zoonotic pathogen and humans are most often infected by consumption of contaminated poultry, water, or raw milk. In addition to acute diarrhea, C. jejuni is associated with a number of post infectious serious sequelae, including Guillain-Barré syndrome (GBS). The molecular basis for the association of C. jejuni with GBS is recognized to be due to the mimicry between lipooligosaccharide (LOS) chains of most C.jejuni strains, such that antibodies directed toward LOS cross react with human peripheral nerves. The association of C. jejuni with GBS poses special problems to vaccine development. The use of any whole cell vaccine approach, although originally evaluated, is precluded due to safety concerns. Similarly, the standard phase 2B challenge that is generally done to evaluate the efficacy of vaccines cannot be performed with C. jejuni strains expressing ganglioside mimics. However, despite the fact that the vast majority of C. jejuni strains express one or more ganglioside mimics in their outer LOS core, there have been some strains described that lack such mimicry. 
A group of american researchers used a hydrogen peroxide (H2O2)-based vaccine platform to produce a protective vaccine against Campylobacter (hydrogen peroxide (H2O2) is used to inactivate the bacteria for vaccine production). Certain strains of Campylobacter express lipooligosaccharide (LOS) that appear to be ganglioside mimics and to mitigate potential safety issues associated with molecular mimicry. The researchers used vaccine strains of Campylobacter [C. coli and C. jejuni] that are genetically incapable of producing ganglioside mimics. H2O2-inactivated Campylobacter vaccination induced an immunodominant antibody response to bacterial flagellin and provided protective immunity against clinical diarrheal disease in a robust nonhuman primate model of naturally occurring C. coli infection despite demonstrating little to no homology within the LOS or capsular polysaccharide (CPS) loci compared to circulating C. coli strains.
The vaccine induced strong antibacterial antibodies to multiple Campylobacter proteins including flagellin and provided up to 83% protection against severe C. coli–associated diarrhea. Whole-genome sequencing of circulating Campylobacter strains revealed little to no homology within lipooligosaccharide or capsular polysaccharide loci with the Campylobacter vaccine strains used in these studies, indicating that vaccine-mediated immunity was not restricted to a single homologous serotype.
These studies not only demonstrate the feasibility of using this natural challenge model but also provide an important proof-of-concept to support the continued development of novel antibacterial vaccines to prevent Campylobacter-associated enteric disease in humans.